Browsing by Subject "CANCER-CELLS"

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  • Perea, Daniel; Guiu, Jordi; Hudry, Bruno; Konstantinidou, Chrysoula; Milona, Alexandra; Hadjieconomou, Dafni; Carroll, Thomas; Hoyer, Nina; Natarajan, Dipa; Kallijärvi, Jukka; Walker, James A.; Soba, Peter; Thapar, Nikhil; Burns, Alan J.; Jensen, Kim B.; Miguel-Aliaga, Irene (2017)
    Expression of the Ret receptor tyrosine kinase is a defining feature of enteric neurons. Its importance is underscored by the effects of its mutation in Hirschsprung disease, leading to absence of gut innervation and severe gastrointestinal symptoms. We report a new and physiologically significant site of Ret expression in the intestine: the intestinal epithelium. Experiments in Drosophila indicate that Ret is expressed both by enteric neurons and adult intestinal epithelial progenitors, which require Ret to sustain their proliferation. Mechanistically, Ret is engaged in a positive feedback loop with Wnt/Wingless signalling, modulated by Src and Fak kinases. We find that Ret is also expressed by the developing intestinal epithelium of mice, where its expression is maintained into the adult stage in a subset of enteroendocrine/enterochromaffin cells. Mouse organoid experiments point to an intrinsic role for Ret in promoting epithelial maturation and regulating Wnt signalling. Our findings reveal evolutionary conservation of the positive Ret/Wnt signalling feedback in both developmental and homeostatic contexts. They also suggest an epithelial contribution to Ret loss-of-function disorders such as Hirschsprung disease.
  • Ferro, Claudio; Florindo, Helena; Santos, Hélder A. (2021)
    Selenium (Se) is an essential element to human health that can be obtained in nature through several sources. In the human body, it is incorporated into selenocysteine, an amino acid used to synthesize several selenoproteins, which have an active center usually dependent on the presence of Se. Although Se shows several beneficial properties in human health, it has also a narrow therapeutic window, and therefore the excessive intake of inorganic and organic Se-based compounds often leads to toxicity. Nanoparticles based on Se (SeNPs) are less toxic than inorganic and organic Se. They are both biocompatible and capable of effectively delivering combinations of payloads to specific cells following their functionalization with active targeting ligands. Herein, the main origin of Se intake, its role on the human body, and its primary biomedical applications are revised. Particular focus will be given to the main therapeutic targets that are explored for SeNPs in cancer therapies, discussing the different functionalization methodologies used to improve SeNPs stability, while enabling the extensive delivery of drug-loaded SeNP to tumor sites, thus avoiding off-target effects.
  • Jarvela, Sally; Rantala, Immo; Rodriguez, Alejandra; Kallio, Heini; Parkkila, Seppo; Kinnula, Vuokko L.; Soini, Ylermi; Haapasalo, Hannu (2010)
  • Metsälä, Olli; Kreutzer, Joose; Högel, Heidi; Miikkulainen, Petra; Kallio, Pasi; Jaakkola, Panu M. (2018)
    BackgroundCells in solid tumours are variably hypoxic and hence resistant to radiotherapy - the essential role of oxygen in the efficiency of irradiation has been acknowledged for decades. However, the currently available methods for performing hypoxic experiments in vitro have several limitations, such as a limited amount of parallel experiments, incapability of keeping stable growth conditions and dependence on CO2 incubator or a hypoxia workstation. The purpose of this study was to evaluate the usability of a novel portable system (Minihypoxy) in performing in vitro irradiation studies under hypoxia, and present supporting biological data.Materials and methodsThis study was conducted on cancer cell cultures in vitro. The cells were cultured in normoxic (similar to 21% O-2) or in hypoxic (1% O-2) conditions either in conventional hypoxia workstation or in the Minihypoxy system and irradiated at dose rate 1.28Gy/min2.9%. The control samples were sham irradiated. To study the effects of hypoxia and irradiation on cell viability and DNA damage, western blotting, immunostainings and clonogenic assay were used. The oxygen level, pH, evaporation rate and osmolarity of the culturing media on cell cultures in different conditions were followed.ResultsThe oxygen concentration in interest (5, 1 or 0% O-2) was maintained inside the individual culturing chambers of the Minihypoxy system also during the irradiation. The radiosensitivity of the cells cultured in Minihypoxy chambers was declined measured as lower phosphorylation rate of H2A.X and increased clonogenic capacity compared to controls (OER similar to 3).Conclusions The Minihypoxy system allows continuous control of hypoxic environment in multiple wells and is transportable. Furthermore, the system maintains the low oxygen environment inside the individual culturing chambers during the transportation and irradiation in experiments which are typically conducted in separate facilities.
  • Hoshian, Sasha; Kankuri, Esko; Ras, Robin H. A.; Franssila, Sami; Jokinen, Ville (2017)
    A top-down scalable method to produce flexible water and blood repellent tubes is introduced. The method is based on replication of overhanging nanostructures from an aluminum tube template to polydimethylsiloxane (PDMS) via atomic layer deposition (ALD) assisted sacrificial etching. The nanostructured PDMS/titania tubes are superhydrophobic with water contact angles 163 +/- 1 degrees (advancing) and 157 +/- 1 degrees (receding) without any further coating. Droplets are able to slide through a 4 mm (inner diameter) tube with low sliding angles of less than 10 degrees for a 35 mu L droplet. The superhydrophobic tube shows up to 5,000 times increase in acceleration of a sliding droplet compared to a control tube depending on the inclination angle. Compared to a free falling droplet, the superhydrophobic tube reduced the acceleration by only 38.55%, as compared to a 99.99% reduction for a control tube. The superhydrophobic tubes are blood repellent. Blood droplets (35 mu L) roll through the tubes at 15 degrees sliding angles without leaving a bloodstain. The tube surface is resistant to adhesion of activated platelets unlike planar control titania and smooth PDMS surfaces.